Exploring Clinical and Neurophysiological Factors Associated with Response to Constraint Therapy and Brain Stimulation in Children with Hemiparetic Cerebral Palsy.

BACKGROUND: Perinatal stroke causes hemiparetic cerebral palsy (HCP) and lifelong disability. Constraint-induced movement therapy (CIMT) and neurostimulation may enhance motor function, but the individual factors associated with responsiveness are undetermined. OBJECTIVE: We explored the clinical and neurophysiological factors associated with responsiveness to CIMT and/or brain stimulation within a clinical trial. METHODS: PLASTIC CHAMPS was a randomized, blinded, sham-controlled trial (n = 45) of CIMT and neurostimulation paired with intensive, goal-directed therapy. Primary outcome was the Assisting Hand Assessment (AHA). Classification trees created through recursive partitioning suggested clinical and neurophysiological profiles associated with improvement at 6-months. RESULTS: Both clinical (stroke side (left) and age >14 years) and neurophysiological (intracortical inhibition/facilitation and motor threshold) were associated with responsiveness across treatment groups with positive predictive values (PPV) approaching 80%. CONCLUSION: This preliminary analysis suggested sets of variables that may be associated with response to intensive therapies in HCP. Further modeling in larger trials is required.

Visualizing a multidrug resistance protein, EmrE, with major bacterial lipids using Brewster angle microscopy.

Understanding lipid-protein interactions to enhance our knowledge of membrane architecture is a critical step in the development of novel therapeutic measures to respond to the drastic rise of drug resistant microorganisms. Escherichia coli contains a small archetypal inner membrane multidrug resistance protein, EmrE, that must multimerize to be functional but this multimerization is difficult to demonstrate in vivo. We studied three major E. coli lipids (phosphatidylethanolamine, phosphatidylglycerol and cardiolipin) that varied in head group structure, acyl chain length and saturation. These were investigated both in the presence and absence of EmrE to determine which lipid(s) EmrE influenced most strongly. Langmuir monolayers and Brewster angle microscopy demonstrated that varying each head group, acyl chain length and saturation contributed to differences in membrane packing and affected lipid-protein associations. Long unsaturated anionic lipids were influenced most strongly by EmrE. Shorter acyl chains initiated string-like formations of EmrE clusters, whereas longer chains contributed to enhance protein clustering. Longer partially unsaturated acyl chains in phosphatidylglycerol showed a significant surface pressure decrease in the presence of the protein, indicating that the monolayer was destabilized. Interestingly, longer unsaturated chains of cardiolipin formed the most stable monolayer in the presence of EmrE. These studies indicate cardiolipin acyl chains that hydrophobically match protein helical lengths stabilize EmrE structural forms.